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Background: In autoimmune disorders, the underlying pathogenic mechanism is the formation of antigen-antibody complexes which trigger an inflammatory response by inducing the infiltration of neutrophils. Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) is a chemokine that recruits and activates neutrophils, thus it could play a pathogenic role in inflammation and autoimmune disorders. Some autistic children have elevated levels of brain specific auto-antibodies. We are the first to evaluate serum expression of ENA-78 and its relation to antineuronal auto-antibodies in autistic children., Methods: Serum ENA-78 and antineuronal auto-antibodies were measured by ELISA test in 62 autistic children aged between 4-11 years and 62 health-matched controls., Results: Serum levels of ENA-78 were significantly higher in autistic children than healthy controls (P < 0.001). Increased serum levels of ENA-78 have been found in 69.35% of autistic patients. In addition, autistic children had significantly higher percent positivity of serum antineuronal auto-antibodies (64.5%) than healthy controls (6.45%), P < 0.001. There was a significant positive association between the positivity of serum antineuronal auto-antibodies and the elevated levels of serum ENA-78 (P < 0.001) in autistic children., Conclusions: Serum levels of ENA-78 were elevated in autistic children and they were significantly associated with the increased levels of serum antineuronal auto-antibodies. However, these data should be treated with caution until further research is conducted to determine the pathogenic role of ENA-78 in autism and its relation to brain specific auto-antibodies that have been found in some autistic children. The possible therapeutic role of ENA-78 antagonist in autistic children should be also studied.

Polyunsaturated fatty acids (PUFAs) are not only essential for energy production, but they also exhibit a range of immunomodulatory properties that progress through T cell mediated events. Autoimmunity may have a pathogenic role in a subgroup of autistic children. This study is the first to investigate the relationship between serum levels of anti-myelin basic protein (anti-MBP) brain-specific auto-antibodies and reduced plasma levels of PUFAs in autistic children. Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA" acids) and serum anti-MBP were measured in 80 autistic children, aged between 4 and 12 years, and 80 healthy-matched children. Autistic patients had significantly lower plasma levels of PUFAs than healthy children. On the other hand, ω6/ω3 ratio (AA/DHA) was significantly higher in autistic patients than healthy children. Low plasma DHA, AA, linolenic and linoleic acids were found in 67.5%, 50%, 40% and 35%, respectively of autistic children. On the other hand, 70% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with increased serum levels of anti-MBP auto-antibodies (75%) had significantly lower plasma DHA (P<0.5) and significantly higher ω6/ω3 ratio (P<0.5) than patients who were seronegative for these antibodies. In conclusions, some autistic children have a significant positive association between reduced levels of plasma DHA and increased serum levels of anti-MBP brain-specific auto-antibodies. However, replication studies of larger samples are recommended to validate whether reduced levels of plasma PUFAs are a mere association or have a role in the induction of the production of anti-MBP in some autistic children., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Gastrointestinal (GI) manifestations are common in autistic children. Polyunsaturated fatty acids (PUFAs) and carnitine are anti-inflammatory molecules and their deficiency may result in GI inflammation. The relationship between the increased frequency of GI manifestations and reduced levels of PUFAs and carnitine was not previously investigated in autistic patients. This study was the first to investigate plasma levels of PUFAs and serum carnitine in relation to GI manifestations in autistic children., Methods: Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA" acids) and serum carnitine were measured in 100 autistic children and 100 healthy-matched children., Results: Reduced levels of serum carnitine and plasma DHA, AA, linolenic and linoleic acids were found in 66%, 62%, 60%, 43% and 38%, respectively of autistic children. On the other hand, 54% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with GI manifestations (48%) had significantly decreased levels of serum carnitine and plasma DHA than patients without such manifestations. In addition, autistic patients with GI manifestations had significantly increased percentage of reduced serum carnitine (91.7%) and plasma DHA levels (87.5%) than patients without such manifestations (42.3% and 38.5%, respectively), (P < 0.001 and P < 0.001%, respectively)., Conclusions: Reduced levels of plasma DHA and serum carnitine levels may be associated with the GI problems in some autistic patients. However, this is an initial report, studies are recommended to invesigate whether reduced levels of carnitine and DHA are a mere association or have a pathogenic role in GI problems in autistic patients.

Background: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt., Results: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane., Conclusions: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs., (© 2015 S. Karger AG, Basel.)

Autism is a neurodevelopmental disorder with unclear pathogenesis. Many clinical observations and hormone studies have suggested the involvement of the neuroprotective hormone ghrelin in autism. The current study aimed to investigate the potential role of ghrelin in autism and to elucidate the associated hormonal dysregulation. This case-control study investigated acyl ghrelin (AG), des-acyl ghrelin (DG), total testosterone (TT), free testosterone (FT), leptin and growth hormone (GH) levels in 31 male children with autism and 28 healthy age and sex-matched controls. Hormone levels were measured in the blood using enzyme-linked immunosorbent assay and chemiluminescence immunoassay kits. AG, DG and GH levels were significantly lower in the autism group than in the control group (p ≤ 0.001, p ≤ 0.005 and p ≤ 0.05, respectively). However, TT, FT and leptin levels were significantly higher in the autism group than in the control group (p ≤ 0.05, p ≤ 0.001 and p ≤ 0.01, respectively). Our results for the first time demonstrate low AG and DG levels in autistic children. Considering the capacity of ghrelin to affect neuroinflammatory and apoptotic processes that are linked to autism, this study suggests a potential role for the hormone ghrelin in the pathogenesis of autism.

Autoimmunity to central nervous system may have a role in the pathogenesis of autism. A subset of anti-ds-DNA antibodies has been recently proved to be pathogenic to the brain as well as to the kidney. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of anti-ds-DNA antibodies in a group of autistic children. The seropositivity of anti-nuclear antibodies (ANA) was also investigated. Serum anti-ds-DNA antibodies and ANA were measured in 100 autistic children, aged between 4 and 11 years, in comparison to 100 healthy-matched children. The seropositivity of anti-ds-DNA antibodies and ANA in autistic children was 34% and 25%, respectively. In addition, 42% of autistic children were seropositive for anti-ds-DNA antibodies and/or ANA. The frequencies of anti-ds-DNA antibodies and ANA in autistic children were significantly higher than that in healthy children (4% and 2%, respectively), (P<0.001 and P<0.001, respectively). Autistic children with a family history of autoimmunity (45%) had significantly higher frequency of serum anti-ds-DNA antibodies (48.9%) than patients without such a history (21.8%), P=0.008. There was a significant positive association between the seropositivity of anti-ds-DNA antibodies and ANA (P<0.001). In conclusion, anti-ds-DNA antibodies and ANA were found in the sera of a subgroup of autistic children. However, replication studies of larger samples are warranted to validate whether these antibodies are a mere association or have a pathogenic role in some autistic children., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is neurodevelopment disorder, characterized by impairment in social interaction, verbal and non-verbal communication and the presence of restricted and repetitive stereotyped behaviors. The condition manifests within the first 3 years of life and persists till adulthood. At present, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. The prevalence of ASD has increased dramatically in the past few decades. According to current estimates from the United States Centers for Disease Control and Prevention (CDC) as many as 1 in 91 children have ASD in USA. Studies from the Middle East on this topic are limited. Autism in Saudi Arabia is slightly higher than reported in the developed countries. Hyperbaric oxygen therapy (HBOT) has been growing in popularity for the treatment of ASD over recent years. However, few studies of its effectiveness have been reported. This article reviews important publications regarding the physiologic and clinical influence of HBO on ASD. Several case series and randomized trials have all proposed that low pressure/ low oxygen concentration hyperbaric treatment can improve the clinical manifestations of autism.

Background: Increasing evidence of autoimmune phenomena in some individuals with autism could represent the presence of altered or inappropriate immune responses in this disorder. The role of the nucleosome in the induction of antibody response in some autoimmune-mediated tissue damage may provide novel targets for treatment. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of antinucleosome-specific antibodies in a group of autistic children., Methods: Serum antinucleosome-specific antibodies were measured by ELISA in 60 autistic children, between the ages of 3 and 12 years, in comparison to 60 healthy children. Autistic severity was assessed using the Childhood Autism Rating Scale (CARS)., Results: Autistic children had significantly higher serum antinucleosome-specific antibodies than healthy children (P <0.001). The seropositivity of antinucleosome-specific antibodies was found in 46.7% of autistic children. Autistic children with a family history of autoimmunity (40%) had a significantly higher frequency of serum antinucleosome-specific antibodies (83.3%) than patients without such a history (22.2%, P <0.001)., Conclusions: Serum levels of antinucleosome-specific antibodies were increased in some autistic children. However, these data should be treated with caution until further investigations are performed with a larger subject population to determine whether these antibodies have a role in the induction of autoimmunity in a subgroup of autistic children. The role of immunotherapy in children with autism should be also studied.

Background: This study aimed to investigate the role of the effectiveness of camel milk (CM) (raw and boiled) on thymus and activation-regulated chemokine (TARC) serum levels and childhood autism rating scale (CARS) score in subjects with autism and compared to placebo group (cow milk)., Methods: Forty-five subjects diagnosed with autism were randomly assigned to receive boiled CM for group I (n = 15), raw CM for group II (n = 15), and placebo for group III (n = 15) for 2 wk. Measures included changes in professionally completed CARS score and blood samples for TARC serum level were taken before and after milk consumption of 500 ml per day in children's regular daily diet., Results: The serum levels of TARC decreased significantly (P = 0.004) in boiled CM and in raw CM group (P = 0.01) too, but no effect was observed (P = 0.68) in placebo group. Furthermore, significant improvements were observed in CARS score (P = 0.04) in raw CM group only. There were no significant relationships between the serum of TARC level and the CARS score, age, or gender for any group., Conclusion: CM administered for 2 wk significantly improved clinical measurements of autism severity and decreased serum level of TARC in autistic children, but subsequent studies are recommended.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in reciprocal social interactions as well as restricted, repetitive and stereotyped patterns of behavior. The etiology of ASD is not well understood, although many factors have been associated with its pathogenesis, such genetic, neurological, environmental and immunological factors. Several studies have reported the production of numerous autoantibodies that react with specific brain proteins and brain tissues in autistic children and alter the function of the attacked brains tissue. In addition, the potential role of maternal autoantibodies to the fatal brain in the etiology of some cases of autism has also been reported. Identification and understanding of the role of brain autoantibodies as biological biomarkers may allow earlier detection of ASD, lead to a better understanding of the pathogenesis of ASD and have important therapeutic implications.

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20 μg/mL respectively for 24 and 72 hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity.

Background: Propionic acid (PA) found in some foods and formed as a metabolic product of gut bacteria has been reported to mimic/mediate the effects of autism. The present study was undertaken to compare the effect of orally administered PA with that of clindamycin-induced PA-microbial producers in inducing persistent biochemical autistic features in hamsters. The neuroprotective potency of carnosine and carnitine supplements against PA toxicity was also investigated., Methods: The following groups were studied. 1. Control group, which received phosphate buffered saline orally, 2. Propionic acid treated group which were given PA at a dose of 250 mg/kg body weight/day for 3 days orally, 3. Clindamycin treated group which received a single dose of the antibiotic orogastrically at a dose of 30 mg/kg on the day of the experiment, 4. Carnosine-treated group which were given carnosine at a dose of 10 mg/kg body weight/day orally for one week, 5. Carnitine treated group given 50 mg/kg body weight/day carnitine orally daily for one week. Group 6. Carnosine followed by PA, Group 7. Carnitine followed by PA. Dopamine, adrenaline and noradrenaline, serotonin and Gamma amino-butyric acid (GABA) were measured in the cortex and medulla of the nine studied groups., Results: PA administration caused significant decrease in the neurotransmitters in the brains of treated hamsters while clindamycin caused a significant decrease only in dopamine in hamster brains (cortex and medulla) and GABA in the cerebral cortex of the treated hamsters. Administration of carnosine and carnitine which are known antioxidants caused no significant changes in the levels of neurotransmitters when administered alone to hamsters. However when administered with PA both carnosine and carnitine restored the altered neurotransmitters to near normal levels., Conclusion: Carnosine and carnitine may be used as supplements to protect against PA neurotoxicity.

Etiology of autism has become an area of a significant controversy. Allergy induced autism is an area of research wherein immune responses to some allergens may play a pathogenic role in autism. Allergy may induce the production of brain specific auto-antibodies in a subgroup of autistic children. We are the first to investigate the possible link between allergic manifestations and serum levels of both anti-myelin basic protein (anti-MBP) and anti-myelin associated glycoprotein (anti-MAG) brain-specific auto-antibodies, which were measured by ELISA method, in 42 autistic children in comparison to 42 healthy-matched children. Allergic manifestations (bronchial asthma, atopic dermatitis and/or allergic rhinitis) were found in 47.6% of autistic patients. Increased serum levels of anti-MBP and anti-MAG auto-antibodies were found in 57.1% and 66.7%, respectively of autistic children. In addition, 78.5% of autistic children had increased serum levels of both anti-MBP and/or anti-MAG auto-antibodies. Autistic patients with allergic manifestations had significantly higher serum levels of anti-MBP and anti-MAG auto-antibodies than those without these manifestations (P<0.001 and P=0.001, respectively). In conclusion, allergy may be a contributing factor to the increased serum levels of anti-MBP and anti-MAG auto-antibodies in some autistic children. Indeed, we need to know more about the links between allergy, immune system and brain in autism for finding new therapeutic modalities in autism., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To investigate the role of an apoptotic marker soluble fatty acid synthase (s-Fas) antigen in children with autism and its correlation to disease severity., Methods: The study was conducted between May 2011 and April 2012 at the Department of Physiology and Autism Research and Treatment Center (ARTC) at King Khalid University Hospital and King Saud University (KSU) in Riyadh, Kingdom of Saudi Arabia. Sixty children were enrolled, 20 as controls, 20 mild, and 20 with severe autism. Plasma samples were analyzed for s-Fas., Results: The levels of s-Fas were significantly higher in autistic children compared with control children (p<0.05). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with mild autism, and there was a positive correlation between s-Fas levels and severe autism (p<0.05)., Conclusion: The s-Fas level is high in Saudi children with severe autism, and can be considered an indicator of disease severity. These findings may offer a new therapeutic or diagnostic tool for children suffering from severe autism.

Background: In some autistic children, there is an imbalance of T helper (Th)1/Th2 lymphocytes toward Th2, which may be responsible for the induction of the production of autoantibodies in these children. Th2 lymphocytes express CCR4 receptors. CCR4 ligands include macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). They direct trafficking and recruitment of Th2 cells. We are the first to measure serum levels of CCR4 ligands in relation to the degree of the severity of autism., Methods: Serum concentrations of MDC and TARC were measured, by quantitative sandwich enzyme immunoassay technique, in 56 autistic children and 32 healthy matched children., Results: Autistic children had significantly higher serum levels of MDC and TARC than healthy controls (P <0.001 and P <0.001, respectively). Children with severe autism had significantly higher serum levels of MDC and TARC than patients with mild to moderate autism (P <0.001 and P = 0.01, respectively). In addition, there were significant positive correlations between CARS and serum levels of both MDC (P <0.001) and TARC (P <0.001) in children with autism. There were significant positive correlations between serum levels of MDC and TARC in autistic children (P <0.001)., Conclusions: Serum levels of CCR4 ligands were elevated in autistic children and they were significantly correlated to the degree of the severity of autism. However, further research is warranted to determine the pathogenic role of CCR4 ligands in autism and to shed light on the therapeutic role of CCR4-ligand antagonism in autistic children.

Aim: To examine the possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats., Methods: Female rats were fed a standard diet and received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception. In study 1, neonatal rats were randomly subjected to blood tests to investigate autism. In study 2, the 1(st) group was fed by the mother after an injection of interferon-γ (IFN-γ) and administration of gliadin. The pups in the 2(nd) group were prevented from accessing maternal milk, injected IFN-γ, administered gliadin, and hand-fed human colostrum. The normal littermates fed by the table mothers were injected with physiological saline and served as normal controls in this study., Results: The protein concentration was higher in group 2 than in group 1 in the duodenum (161.6 ± 9 and 135.4 ± 7 mg/g of tissue, respectively, P < 0.01). A significant increase (P < 0.001) in body weight was detected in human colostrum-treated pups on post natal day (PND) 7 and 21 vs suckling pups in group 1. A delay in eye opening was noticed in the treated rats in group 1 on PND 13 compared with the control group and group 2. Administration of a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception resulted in significantly reduced calcium and vitamin D levels in study 1 compared with the control groups (P < 0.001). However, human colostrum uptake inhibited increases in the level of transglutaminase antibody in autistic pups with coeliac disease., Conclusion: The effects of early-life nutrition and human colostrum on the functional maturation of the duodenal villi in autistic rats with coeliac disease that might limit or prevent the coeliac risk with autism.

The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Extensive studies have demonstrated that oxidative stress plays a vital role in the pathology of several neurological diseases, including autism spectrum disorder (ASD); those studies proposed that GSH and antioxidant enzymes have a pathophysiological role in autism. Furthermore, camel milk has emerged to have potential therapeutic effects in autism. The aim of the current study was to evaluate the effect of camel milk consumption on oxidative stress biomarkers in autistic children, by measuring the plasma levels of glutathione, superoxide dismutase, and myeloperoxidase before and 2 weeks after camel milk consumption, using the ELISA technique. All measured parameters exhibited significant increase after camel milk consumption (P < 0.5). These findings suggest that camel milk could play an important role in decreasing oxidative stress by alteration of antioxidant enzymes and nonenzymatic antioxidant molecules levels, as well as the improvement of autistic behaviour as demonstrated by the improved Childhood Autism Rating Scale (CARS).

Background: Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies., Aim: This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism., Methods: Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale., Results: Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001., Conclusions: Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Aside from the skeletal health affection, vitamin D deficiency has been implicated as a potential environmental factor triggering for some autoimmune disorders. Vitamin D might play a role in the regulation of the production of auto-antibodies. Immunomodulatory effects of vitamin D may act not only through modulation of T-helper cell function, but also through induction of CD4(+)CD25(high) regulatory T-cells. We are the first to investigate the relationship between serum levels of 25-hydroxy vitamin D and anti-myelin-associated glycoprotein (anti-MAG) auto-antibodies in autistic children., Methods: Serum levels of 25-hydroxy vitamin D and anti-MAG auto-antibodies were measured in 50 autistic children, aged between 5 and 12 years, and 30 healthy-matched children. Serum 25-hydroxy vitamin D levels 10-30 ng/mL and < 10 ng/mL were defined as vitamin D insufficiency and deficiency, respectively., Results: Autistic children had significantly lower serum levels of 25-hydroxy vitamin D than healthy children (P < 0.001) with 40% and 48% being vitamin D deficient and insufficient, respectively. Serum 25-hydroxy vitamin D had significant negative correlations with Childhood Autism Rating Scale (P < 0.001). Increased levels of serum anti-MAG auto-antibodies were found in 70% of autistic patients. Serum 25-hydroxy vitamin D levels had significant negative correlations with serum levels of anti-MAG auto-antibodies (P < 0.001)., Conclusions: Vitamin D deficiency was found in some autistic children and this deficiency may contribute to the induction of the production of serum anti-MAG auto-antibodies in these children. However, future studies looking at a potential role of vitamin D in the pathophysiology and treatment of autism are warranted.

Background: The T-helper (Th)1/Th2 dichotomy dominated the field of immune regulation until interleukin (IL)-17-expressing T cells (Th17) were proposed to be a third lineage of helper T cells, the key players in the pathogenesis of autoimmune disorders. Autoimmunity to brain tissue may play a pathogenic role in autism. IL-17A is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. The aim of this study was to measure serum levels of IL-17A in relation to the degree of the severity of autism., Methods: Serum IL-17A levels were measured by ELISA in 45 children with autism and 40 matched healthy controls., Results: Children with autism had significantly higher serum IL-17A levels than healthy controls (P <0.001), with increased serum levels of IL-17A found in 48.9% of the autism group. Patients with severe autism had significantly higher serum IL-17A levels than those with mild to moderate autism (P=0.01), and raised serum IL-17A levels were significantly more common in children with severe autism (67.9%) than in those with mild to moderate autism (17.6%), P=0.001., Conclusions: Serum IL-17A levels were raised in the group with autism, and the levels correlated significantly with the severity of autism. This is the first study to measure levels of IL-17A in relation to the severity of autism, to our knowledge. Further research, with a larger subject population, is warranted to determine whether the increase of serum IL-17A levels plasma has a pathogenic role in autism, and whether anti- IL-17A therapy could be useful.

Objective: To investigate the role of 2 angiogenic/neurogenic growth factors, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in Saudi children with autism., Methods: The study included a total of 60 children that included 20 controls and 40 patients with a confirmed diagnosis of autism. The study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, and in the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between May 2010 and April 2011. Collected blood plasma samples were analyzed for VEGF and PDGF., Results: The levels of VEGF showed a non-significant change in autistic children compared with the control children (p=0.065). The levels of PDGF were significantly higher in autistic children compared with the control children (p=0.01). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with children with mild autism (p=0.001), and it was not correlated to the severity of the disorder., Conclusion: A rise in PDGF may contribute to the pathophysiology of the disorder, either alone or in synergy with other neurotrophic factors to induce an angiogenic-neuroprotective effect. Plasma VEGF has no causative or compensatory contribution to the pathology of this disorder.

Background: S100B is a calcium-binding protein that is produced primarily by astrocytes. Increased serum S100B protein levels reflect neurological damage. Autoimmunity may have a role in the pathogenesis of autism in some patients. Autoantibodies may cross the blood-brain barrier and combine with brain tissue antigens, forming immune complexes and resulting in neurological damage. We are the first to investigate the relationship between serum levels of S100B protein, a marker of neuronal damage, and antiribosomal P protein antibodies in autistic children., Methods: Serum S100B protein and antiribosomal P antibodies were measured in 64 autistic children in comparison to 46 matched healthy children., Results: Autistic children had significantly higher serum S100B protein levels than healthy controls (P < 0.001). Children with severe autism had significantly higher serum S100B protein than patients with mild to moderate autism (P = 0.01). Increased serum levels of antiribosomal P antibodies were found in 40.6% of autistic children. There were no significant correlations between serum levels of S100B protein and antiribosomal P antibodies (P = 0.29)., Conclusions: S100B protein levels were elevated in autistic children and significantly correlated to autistic severity. This may indicate the presence of an underlying neuropathological condition in autistic patients. Antiribosomal P antibodies may not be a possible contributing factor to the elevated serum levels of S100B protein in some autistic children. However, further research is warranted to investigate the possible link between serum S100B protein levels and other autoantibodies, which are possible indicators of autoimmunity to central nervous system in autism.

Background: There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism., Methods: The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups., Results: We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio., Conclusion: A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.

The etiology of autism spectrum disorders (ASD) is not well known but oxidative stress has been suggested to play a pathological role. We report here that the serum levels of Sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. By using the whole blood or polymorphonuclear leukocytes, we demonstrated that autistic children produced a significantly higher level of oxygen free radicals (OFR). In addition, we found significantly higher levels of serum SHH protein in children with mild as well as severe form of autism. We also found that the serum level of BDNF was significantly reduced in autistic children with mild form of the disorder but not with severe form of the disorder. Our findings are the first to report a correlation between SHH, BDNF and OFR in autistic children, suggesting a pathological role of oxidative stress and SHH in autism spectrum disorders.

Objectives: We examined whether plasma concentrations of amyloid beta (Aβ) as protein derivatives play a central role in the etiology of autistic features., Design and Methods: Concentrations of human Aβ (1-42), Aβ (1-40), and Aβ (40/42) in the plasma of 52 autistic children (aged 3-16 years) and 36 age-matched control subjects were determined by using the ELISA technique and were compared., Results: Compared to control subjects, autistic children exhibited significantly lower concentrations of both Aβ (1-40) and Aβ (1-42) and lower Aβ (40/42) concentration ratio. Receiver operating characteristics curve (ROC) analysis showed that these measurements of Aβ peptides showed high specificity and sensitivity in distinguishing autistic children from control subjects., Conclusions: Lower concentrations of Aβ (1-42) and Aβ (1-40) were attributed to loss of Aβ equilibrium between the brain and blood, an imbalance that may lead to failure to draw Aβ from the brain and/or impairment of β- and γ- secretase's concentration or kinetics as enzymes involving in Aβ production.

Background: Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in some patients. We are the first to measure serum neurokinin A levels in autistic children. The relationship between serum levels of neurokinin A and anti-ribosomal P protein antibodies was also studied., Methods: Serum neurokinin A and anti-ribosomal P protein antibodies were measured in 70 autistic children in comparison to 48 healthy-matched children., Results: Autistic children had significantly higher serum neurokinin A levels than healthy controls (P < 0.001). Children with severe autism had significantly higher serum neurokinin A levels than patients with mild to moderate autism (P < 0.001). Increased serum levels of neurokinin A and anti-ribosomal P protein antibodies were found in 57.1% and 44.3%, respectively of autistic children. There was significant positive correlations between serum levels of neurokinin A and anti-ribosomal P protein antibodies (P = 0.004)., Conclusions: Serum neurokinin A levels were elevated in some autistic children and they were significantly correlated to the severity of autism and to serum levels of anti-ribosomal P protein antibodies. However, this is an initial report that warrants further research to determine the pathogenic role of neurokinin A and its possible link to autoimmunity in autism. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, should also be studied in autism.

Background: Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects., Methods: 20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined., Results: Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects., Conclusion: The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism.

Objectives: Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the relationship amongst absolute and relative concentrations of K+, Na+, Ca2+, Mg2+ and/or proinflammatory and proapoptotic biomarkers., Materials and Methods: Na+, K+, Ca2+, Mg2+, Na+/K+, Ca2+/Mg2+ together with IL6, TNFα as proinflammatory cytokines and caspase3 as proapoptotic biomarker were determined in plasma of 25 Saudi autistic male patients and compared to 16 age and gender matching control samples., Results: The obtained data recorded that Saudi autistic patients have a remarkable lower plasma caspase3, IL6, TNFα, Ca2+ and a significantly higher K+ compared to age and gender matching controls. On the other hand both Mg2+ and Na+ were non-significantly altered in autistic patients. Pearson correlations revealed that plasma concentrations of the measured cytokines and caspase-3 were positively correlated with Ca2+ and Ca2+/K+ ratio. Reciever Operating Characteristics (ROC) analysis proved that the measured parameters recorded satisfactory levels of specificity and sensitivity., Conclusion: Alteration of the selected measured ions confirms that oxidative stress and defective mitochondrial energy production could be contributed in the pathogenesis of autism. Moreover, it highlights the relationship between the measured ions, IL6, TNFα and caspase3 as a set of signalling pathways that might have a role in generating this increasingly prevalent disorder. The role of ions in the possible proinflammation and proapoptic mechanisms of autistics' brains were hypothesized and explained.

Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism., Methods: Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children., Results: Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11., Conclusions: Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

Background: One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism., Methods: Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children., Results: Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39)., Conclusions: Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder.

Background: Autoimmunity to the central nervous system (CNS) may play a pathogenic role in a subgroup of patients with autism. This study aimed to investigate the frequency of serum anti-ganglioside M1 auto-antibodies, as indicators of the presence of autoimmunity to CNS, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism., Methods: Serum anti-ganglioside M1 antibodies were measured, by ELISA, in 54 autistic children, aged between 4 and 12 years, in comparison to 54 healthy-matched children. Autistic severity was assessed by using the Childhood Autism Rating Scale (CARS)., Results: Autistic children had significantly higher serum levels of anti-ganglioside M1 antibodies than healthy children (P < 0.001). The seropositivity of anti-ganglioside M1 antibodies was found in 74% (40/54) of autistic children. Serum levels of anti-ganglioside M1 antibodies were significantly higher in autistic children with severe autism (63%) than those with mild to moderate autism (37%), P = 0.001. Moreover, serum anti-ganglioside M1 antibodies had significant positive correlations with CARS (P < 0.001)., Conclusions: Serum levels of anti-ganglioside M1 antibodies were increased in many autistic children. Also, their levels had significant positive correlations with the degree of the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the possible etiopathogenic role of anti-ganglioside M1 auto-antibodies in autism. The role of immunotherapy in autistic patients who have increased serum levels of anti-ganglioside M1 antibodies should also be studied.

Objective: To examine gluten sensitivity through the measurement of anti-gliadin antibody (IgA and IgG), anti-endomysial antibody (endo-IgA), anti-reticulin antibody (IgG) and anti-transglutamase antibody (IgG) levels in blood samples of autistic in the Riyadh area., Methods: The study took place in the Department of Physiology, Faculty of Medicine, King Saud University, Riyadh between September 2003 and April 2004. Thirty-three autistic children, from the Riyadh area participated in the study, all with confirmed diagnosis according to E-2 diagnostic criteria for autistic spectrum disorders. Anti-gliadin antibody (IgA and IgG), anti-endomysial antibody (endo-IgA), anti-reticulin antibody (IgG) and anti-transglutamase antibody (IgG), were measured by the enzyme linked immunosorbent assay method., Results: Thirty-three autistic children with confirmed diagnosis (30 males and 3 females) participated in the study. A significant percentage of autistic children complained of constipation as compared to control. None of the autistic examined were positive for any of the antibodies tested, including anti-gliadin antibody (IgA and IgG), anti-endomysial antibody (endo-IgA), anti-reticulin antibody (IgG) and anti-transglutamase antibody (IgG). The same results were reached with the control group., Conclusion: The present study demonstrated that gluten sensitivity is not a major cause in those autistic children examined.

Objective: It is a well documented fact that under stress conditions the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are stimulated. This results in a series of neural and endocrine adaptations known as the stress response. The current study assessed the effects of acute cold stress on adrenomedullin (ADM) levels in plasma and peripheral tissues (kidneys and heart) of rats, as well as on blood glucose, cholesterol, triglycerides (TG), total proteins both before and after intraperitoneal administration of each of the following: vitamin-E, L-arginine, forskolin and L-NAME., Methods: The current study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, Saudi Arabia, between September 2003 and March 2004. We observed 6 groups of Wistar rats for their plasma ADM, tissue plasminogen activator (t-PA), total protein, glucose and cholesterol levels. Following exposure to cold stress (-10 degree C for 3 hours)., Results: Acute cold stress produced a significant increase in ADM levels in plasma, heart and kidney tissues of rats. Furthermore, acute cold stress produced a reduction in cholesterol and plasma protein levels. On the other hand, acute cold stress caused an increase in TG, glucose plasma levels and tissue plasminogen activator (t-PA). We found hormonal and metabolic changes caused by cold exposure to be decreased or even prevented after vitamin E treatment or after changing nitric oxide (NO) level by L-arginine or L-NAME treatment., Conclusion: The results suggest a regulatory or protective role for ADM in counteracting HPA activation following a variety of physiological and psychological stressors. Oxidative stress or changes in intracellular signals as NO, cyclic-AMP may play a role in explaining some of the metabolic and hormonal changes occurring during acute cold stress.

Objective: Autism is a neurodevelopmental disorder with unknown etiology. The etiology of autism is complex, and the underlying pathologic mechanisms are unknown. This study tests the autoimmune mechanisms in the pathogenesis for autism in autistic children in the Riyadh area., Methods: The study took place in the Riyadh area of the Kingdom of Saudi Arabia between September 2003 and April 2004. Sixty-five autistic children, with a confirmed diagnosis according to E-2 diagnostic criteria for autistic spectrum disorders, participated in the study. Serological examination of antibodies to measles, mumps, rubella (MMR), and myelin basic protein (MBP) was carried out in autistic and control children., Results: The level of MBP antibodies was significantly higher in autistic children as compared to controls (p<0.01). Furthermore, the level of antibodies to measles but not mumps or rubella was significantly higher in autistics compared to the control group (p<0.05). Moreover, 82% of autistic sera positive for measles IgG was also positive for MBP., Conclusion: The current study supports the hypothesis that autoimmunity plays a role in the pathogenesis of autism. However, results from the current study are not enough to support that immunization by MMR is playing a role in the autoimmune process in autistism.

Objective: Autism a childhood neurodevelopmental disorder, with onset prior to 36 months old. The etiology of autism is complex, and usually, the underlying pathologic mechanisms are unknown. Recently, alteration in heavy metals and trace elements had some interest. The aim of the present study is to examine levels of trace elements and heavy metals in hair samples, of autism spectrum disorders in the Riyadh area., Methods: The study was conducted in Riyadh area, Kingdom of Saudi Arabia between September 2003 and April 2004. Seventy-seven autistic children participated in the study, all with confirmed diagnosis according to E-2 diagnostic criteria for autistic spectrum disorders. Hair samples were analyzed by atomic absorption spectrophotometer. The measurements of 9 heavy metals (lead, mercury, aluminum, arsenic, barium, cadmium, nickel, antimony and strontium), and 11 trace elements (sodium, calcium, chromium, copper, iron, magnesium, manganese, zinc, cobalt, selenium and molybdenum) was carried out., Results: The current study showed significantly higher levels of toxic heavy metals mercury, lead, arsenic, antimony and cadmium in autistic spectrum disorders as compared to the control children. Moreover, hair samples from children with autistic spectrum disorders contained significantly lower concentrations of calcium, copper, chromium, manganese, iron and cobalt, as compared to normal children. In addition, we found a significantly higher incidence of social withdrawal, sleeping and eating disorders, speech and language disorders among autism spectrum disorders as compared to controls., Conclusion: The present study demonstrated alteration in levels of toxic heavy metals and essential trace elements in children with autistic spectrum disorders as compared to normal children. This suggests a possible pathophysiological role of heavy metals and trace elements in the genesis of symptoms of autism spectrum disorders, such as social withdrawal, eating and sleeping disorders. In turn, those children with autistic spectrum disorders might benefit from chelating therapy for heavy metal poisoning and supplementation of essential trace elements.

Objective: Abnormal inflammatory immune response might contribute to autism. Pro-inflammatory cytokines could induce some of the symptoms and signs of autism. Such as, social withdrawal eating and sleep disturbance. The aim of the current study was to examine whether autism spectrum disorders in Riyadh area are accompanied by activation of the pro-inflammatory response system., Methods: The study was conducted in the Riyadh area between September 2003 and April 2004. Seventy-seven autistic child from the Riyadh area participated in the study, with confirmed diagnosis according to E-2 diagnostic criteria for autistic spectrum disorders. The parents/guardians filled a simple related questionnaire, then serum concentrations of tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1) and interleukin-6 (IL-6) were measured in 65 autistic, 8 attention deficit disorder, 2 children with Rett`s syndrome and 2 children with Asperger syndrome. The results were compared to age, and sex matched control children., Results: This study showed a significantly increased production of TNF-a, IL-1 and IL-6 from the sera of autistic, attention deficit disorder, Rett`s syndrome and Asperger syndrome children. There was no correlation between TNF-a, IL-1 or IL-6 and the degree of autism or the age of the affected child. Significant higher incidence of social withdrawal, sleeping and eating disorders were found among autism spectrum disorders compared to control., Conclusion: These results suggest that autism may be accompanied by an activation of the macrophages. It is hypothesized that increased production of pro-inflammatory cytokines could play a role in the pathophysiology of autism spectrum disorders, such as social withdrawal, eating and sleeping disorders.

Objective: The aim of the current study is to assess plasma levels of oxytocin and vasopressin in autistic children. Also, to correlate plasma levels of those neuropeptides to the degree of autism and age of the affected child. An additional aim is to investigate the role of Pitocin induction in the genesis of autism., Methods: The study was conducted in Riyadh, Kingdom of Saudi Arabia between September 2003 and April 2004. Seventy-seven autistic child from Riyadh area participated in the study, with the confirmed diagnosis according to DSM-IV diagnostic criteria of autism. The parents/guardians filled a simple related questionnaire, then plasma oxytocin and vasopressin levels were measured in autistic and control children., Results: Results showed a statistically significant lower plasma level of oxytocin and vasopressin in autistic children as compared to controls. There was no significant correlation between the degree of autism, or the age of the affected child and plasma levels of oxytocin or vasopressin. There was a higher incidence of Pitocin-induced labor among autistics as compared to normal., Conclusion: Data in this study prove that oxytocin and vasopressin plasma levels were reduced in autistic children which, might be related to abnormal social behavior in autistic children. Higher rates of Pitocin induction were found among the autistic group. The data supports an association between exogenous exposure to oxytocin and neurodevelopmental abnormalities. Further clinical studies are recommended to explore the possible therapeutic effects of oxytocin and vasopressin in autism.

The adenosine A2A receptor agonist CGS21680 (50, 100 and 200 microg/ml), the phosphodiserease type IV (PDE IV) inhibitor Rolipram (50, 100 and 200 microg/ml) and, ATP-sensitive K+ channels activator Cromakalim (30 and 40 microg/ml), when added separately, inhibit oxygen free radicals production from isolated human polymorphoneuclear leukocytes (PMNLs), stimulated with phorbol myristate acetate (PMA), in a dose dependent manner. When both CGS21680 and Rolipram were combined, in vitro, the inhibitory effect on PMNLs free radicals production was synergistic. On the other hand, when both the ATP-sensitive K+ channels opener (KATP) Cromakalim and the type IV PDE inhibitor Rolipram were combined, produced negative synergism (the inhibitory effect of both drugs disappeared). Furthermore, CGS21680, Rolipram, Cromakalim and Forskolin produced no significant inhibitory effect on PMNLs aggregation when added separately. But when various combinations of the above drugs were used, produced significant inhibition of aggregation. Only CGS21680 exhibited a scavenging effect on free radicals production. From the above results, combination of adenosine A2A agonists and type IV PDE inhibitors could serve as potentially novel anti-inflammatory drugs. Furthermore, ATP-sensitive K+ channels activators should be considered for further investigation as anti-inflammatory drug., (Copyright 2004 Elsevier Ltd.)

Objective: The relationship between male and female sex hormones (testosterone, estradiol and progesterone), personality characters and professional status was studied., Methods: The study was conducted in Riyadh City, Kingdom of Saudi Arabia between September 2003 and May 2003. The participants completed a questionnaire consisting of personal information regarding age, profession, educational level and medical history. Then the participant went through an adjective checklist. Hormones were determined from blood samples provided by the participant., Results: The result indicated that the higher the professional levels, the higher was the testosterone concentrations, but not estradiol or estrogen concentration. Furthermore, females with higher testosterone concentration (university lecturers, bank managers, bank employee, medical doctors and technical workers) identify themselves as independent, strong, assertive, impulsive, resourceful, spontaneous, uninhibited, rational, patient and arguing. Whereas, females with lower testosterone concentrations (housewives and clerical workers) view themselves as civilized, socialized, calm, quite, sentimental, shy, nice, sensitive, warmhearted, sympathetic, thoughtful, warm, practical and kind., Conclusion: The current study emphasizes the positive relationship between strong personality characters, high professional status and male sex hormone level (testosterone) in females.

Several disease conditions are believed to be related to oxygen free radical formation including a number of neurodegenerative disorders. Therapy using free radical scavengers (antioxidants) has been used to prevent, delay or modify the progress of many neurological disorders. The optimum antioxidant therapeutic options have to be tailored and modified individually. This is because the biochemistry of oxidative pathophysiology is still a complex matter. In this review the role of oxidative stress and the potential therapeutic effect of some antioxidants is discussed in a number of neurodegenerative disorders including Alzheimer disease, Parkinson`s disease and multiple sclerosis.